Gains of 13q are correlated with a poor prognosis in liposarcoma

Abstract

Liposarcomas are a phenotypical heterogenous group of tumors divided into four main subtypes: welldifferentiated, dedifferentiated, myxoid/round cell, and pleomorphic. The aim of this study was to compare DNA sequence copy number changes of these subtypes as investigated by comparative genomic hybridization in 36 patients. Comparative genomic hybridization revealed genomic imbalances in tumors of 27 patients (mean 5.6 imbalances per tumor). The most frequent gains were within single regions of 1q, 12q, and 13q. We found a significant correlation of poor overall survival and gain of 13q21 (P ¼ 0.0221), 13q22 (P ¼ 0.0341), 13q31 (P ¼ 0.0410), and 13q32 (P ¼ 0.0074). The univariate Cox regression analysis revealed an increased risk of tumorrelated death for patients whose liposarcomas possess with gains of 13q21 and 13q32 simultaneously (P ¼ 0.010; RR ¼ 7.1; 95% CI 1.6-31.7). Furthermore, 12 high-level amplifications were found in tumors of seven patients. In four cases 12q14-q15 and in two cases 13q32-q33 were amplified. We identified in different liposarcoma subtypes characteristic genomic changes: Gains and high-level amplifications of 12q occurred in all 11 investigated well-differentiated liposarcomas, and these changes were often present simultaneously with gains of 1q (mean 5.5 changes). In the two dedifferentiated liposarcomas, gains of 1q in both liposarcomas, and a high-level amplification of 13q were striking. Only eight of the 17 patients with myxoid/round cell liposarcomas showed changes in DNA copy number (mean 3.4 imbalances). In four of these eight cases gains of 13q occurred. The six pleomorphic liposarcomas possessed the most frequent genomic imbalances (mean number 16.3) of all liposarcoma subtypes investigated. These imbalances were in almost all chromosomal regions detected predominantly as over-representations of chromosomes 1, 5p, 13q, and 22q. Summarizing, all subtypes but well-differentiated liposarcomas showed gains of 13q, which were associated with a poor prognosis. Modern Pathology (2005) 18, 638-644, advance online publication, 12 November 2004; doi:10.1038/modpathol.3800326Keywords: CGH; gain of 13q; liposarcoma subtypes; poor prognosis Liposarcomas are the most common soft-tissue sarcomas in adults and account for approximately 20% of all mesenchymal malignancies. The WHO classification divides liposarcomas into four main histological subtypes that are correlated with degree of malignancy: well-differentiated, dedifferentiated, myxoid/round cell, and pleomorphic liposarcomas. 1 Well-differentiated liposarcomas are tumors of low degree of malignancy. When located in the subcutis, they are usually cured by local surgical resection and rarely recur. 2 Comprising 40-45% of all liposarcomas, the well-differentiated liposarcomas are thus the largest subgroup of adipocytic malignancies. Cytogenetic characteristics of well-differentiated liposarcomas are rings as well as giant marker chromosomes that contain amplified genetic material derived from chromosome region 12q13-q15 and, alternative...

Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways

“…Moreover, the occurrence of 1q22-q24 overrepresentation was shown to be associated with the dedifferentiation of a WDLS to a highly malignant metastatic osteosarcoma [31]. Yet, contrasting to our data on infrequent gains of 1q21-q24 in WDLS, overrepresentations of 1q21-q22 were also described in subsets of WDLS of other series [3,21].…”

“…In PLLS, complex chromosomal changes without specific rearrangements have been detected in karyotypic analyses [13,18]. Yet, in previous comparative CGH studies we and others identified distinct and recurrent chromosomal imbalances in PLLS [19][20][21][22].…”

c‐Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme

“…In addition to the six WDLPSs with normal c-Jun copy number in our study, at least 92 pure WDLPSs have been previously studied by comparative genomic hybridization (traditional or array-based) [4,[8][9][10][11][12][13][14][15][16][17][18]. In these studies, high-level amplification of the c-Jun locus at 1p32 was never observed; only one case of low-level copy number gain involving 1p31 to 1p36 was reported [13].…”

Soft tissue sarcomas with complex genomic profiles

“…Idbaih et al [54] observed that chromosome imbalances encountered in PLPS were very similar to those observed in their series of myxofibrosarcoma, and that the two histotypes, taken together, can be distinguished from other pleomorphic sarcomas and more specifically from LMS. In the study of Schmidt et al [62], patients with gains of 13q (i.e., 13q21, 13q22, 13q31, and 13q32) experienced shortened survivals as compared to those lacking these gains.…”